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Conserved domains on  [gi|1370465470|ref|XP_024305460|]
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protein PALS1 isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
GuKc smart00072
Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to ...
 457-627 1.96e-50

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.


:

Pssm-ID: 214504 [Multi-domain]  Cd Length: 174  Bit Score: 172.48  E-value: 1.96e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  457 GQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSG 536
Cdd:smart00072   4 GKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVAEKG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  537 KICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKnPKPEELREIIEKTREMEQNNgHYFDTAIVNSDLDK 616
Cdd:smart00072  84 KHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQRGT-ETSERIQKRLAAAQKEAQEY-HLFDYVIVNDDLED 161

                          170
                   ....*....|.
gi 1370465470  617 AYQELLRLINK 627
Cdd:smart00072 162 AYEELKEILEA 172
PDZ_MPP5-like cd06798
PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related ...
 221-300 2.34e-49

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


:

Pssm-ID: 467259 [Multi-domain]  Cd Length: 79  Bit Score: 166.37  E-value: 2.34e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDiPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06798     1 KIVRIEKTRE-PLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLIP 79
SH3_MPP5 cd12036
Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); ...
 315-377 2.70e-42

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212969  Cd Length: 63  Bit Score: 146.40  E-value: 2.70e-42
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd12036     1 HVRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAYREGEEDNQSLAGLIPSKS 63
L27_N pfam09060
L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the ...
 89-136 7.74e-21

L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the establishment of cell polarity in epithelial cells. Each L27_N domain consists of three alpha-helices, the first two of which form an antiparallel coiled-coil. Two L27 domains come together to form a four-helical bundle with the antiparallel coiled-coils formed by the first two helices. The third helix of each domain forms another coiled-coil packing at one end of the four-helix bundle, creating a large hydrophobic interface: the hydrophobic interactions are the major force that drives heterodimer formation.


:

Pssm-ID: 462666  Cd Length: 48  Bit Score: 85.84  E-value: 7.74e-21
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370465470  89 EIEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNKDFQNAFKIHNAIT 136
Cdd:pfam09060   1 ELEELLQSLKHVQHCLTDSQSQQDVELILQLLQKEDFQNAFSIHNAVS 48
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
155-203 1.81e-07

domain in receptor targeting proteins Lin-2 and Lin-7;


:

Pssm-ID: 197794  Cd Length: 53  Bit Score: 47.89  E-value: 1.81e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370465470  155 LAQEVQTVLKP--VHHKEGQELTALLNTPHIQALLLAHDKVAEQEMQLEPI 203
Cdd:smart00569   2 RLLELLEELQSllSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLP 52
 
Name Accession Description Interval E-value
GuKc smart00072
Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to ...
 457-627 1.96e-50

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.


Pssm-ID: 214504 [Multi-domain]  Cd Length: 174  Bit Score: 172.48  E-value: 1.96e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  457 GQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSG 536
Cdd:smart00072   4 GKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVAEKG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  537 KICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKnPKPEELREIIEKTREMEQNNgHYFDTAIVNSDLDK 616
Cdd:smart00072  84 KHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQRGT-ETSERIQKRLAAAQKEAQEY-HLFDYVIVNDDLED 161

                          170
                   ....*....|.
gi 1370465470  617 AYQELLRLINK 627
Cdd:smart00072 162 AYEELKEILEA 172
PDZ_MPP5-like cd06798
PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related ...
 221-300 2.34e-49

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467259 [Multi-domain]  Cd Length: 79  Bit Score: 166.37  E-value: 2.34e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDiPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06798     1 KIVRIEKTRE-PLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLIP 79
Guanylate_kin pfam00625
Guanylate kinase;
444-628 3.16e-49

Guanylate kinase;


Pssm-ID: 395500  Cd Length: 182  Bit Score: 169.87  E-value: 3.16e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 444 RKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYG 523
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 524 TSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKnpkpEELREIIEKTREMEQNNGH 603
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKGRGK----EQEEKINKRMAAAEQEFQH 156

                         170       180
                  ....*....|....*....|....*.
gi 1370465470 604 Y-FDTAIVNSDLDKAYQELLRLINKL 628
Cdd:pfam00625 157 YeFDVIIVNDDLEEAYKKLKEALEAE 182
guanyl_kin TIGR03263
guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP ...
 446-627 1.83e-42

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]


Pssm-ID: 213788  Cd Length: 179  Bit Score: 151.11  E-value: 1.83e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 446 RPIILIGPQNCGQNELRQRLMnKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTS 525
Cdd:TIGR03263   1 LLIVISGPSGAGKSTLVKALL-EEDPNLKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 526 IDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNpKPEELREIIEKTR-EMEQnnGHY 604
Cdd:TIGR03263  80 KSPVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILPPSLEELERRLRKRGTD-SEEVIERRLAKAKkEIAH--ADE 156

                         170       180
                  ....*....|....*....|...
gi 1370465470 605 FDTAIVNSDLDKAYQELLRLINK 627
Cdd:TIGR03263 157 FDYVIVNDDLEKAVEELKSIILA 179
SH3_MPP5 cd12036
Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); ...
 315-377 2.70e-42

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212969  Cd Length: 63  Bit Score: 146.40  E-value: 2.70e-42
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd12036     1 HVRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAYREGEEDNQSLAGLIPSKS 63
GMPK cd00071
Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), ...
 447-622 4.02e-38

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.


Pssm-ID: 238026  Cd Length: 137  Bit Score: 137.66  E-value: 4.02e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 447 PIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSI 526
Cdd:cd00071     1 LIVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 527 DSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPsqerlrallakegknpkpeelreiiektremeqnnghyfD 606
Cdd:cd00071    81 AAVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP---------------------------------------D 121

                         170
                  ....*....|....*.
gi 1370465470 607 TAIVNSDLDKAYQELL 622
Cdd:cd00071   122 YVIVNDDLEKAYEELK 137
PLN02772 PLN02772
guanylate kinase
 443-625 3.57e-35

guanylate kinase


Pssm-ID: 215414 [Multi-domain]  Cd Length: 398  Bit Score: 137.28  E-value: 3.57e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 443 NRKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLY 522
Cdd:PLN02772  133 NAEKPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLY 212

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 523 GTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNPKPEELREIIEKTREMEQNNG 602
Cdd:PLN02772  213 GTSIEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRARGTETEEQIQKRLRNAEAELEQGKS 292

                         170       180
                  ....*....|....*....|....
gi 1370465470 603 HY-FDTAIVNSDLDKAYQELLRLI 625
Cdd:PLN02772  293 SGiFDHILYNDNLEECYKNLKKLL 316
Gmk COG0194
Guanylate kinase [Nucleotide transport and metabolism];
448-633 5.81e-33

Guanylate kinase [Nucleotide transport and metabolism];


Pssm-ID: 439964  Cd Length: 190  Bit Score: 125.18  E-value: 5.81e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 448 IILIGPQNCGQNELRQRLMnKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSID 527
Cdd:COG0194     5 IVLSGPSGAGKTTLVKALL-ERDPDLRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 528 SVRQVINSGKICLLSLRTQSLKTLRNSdLKPYI-IFIAPPSQERLRALLAKEGknpkpEELREIIEK-----TREMEQnn 601
Cdd:COG0194    84 EVEEALAAGKDVLLEIDVQGARQVKKK-FPDAVsIFILPPSLEELERRLRGRG-----TDSEEVIERrlakaREELAH-- 155

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1370465470 602 GHYFDTAIVNSDLDKAYQELLRLI--NKLDTEPQ 633
Cdd:COG0194   156 ADEFDYVVVNDDLDRAVEELKAIIraERLRRERQ 189
L27_N pfam09060
L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the ...
 89-136 7.74e-21

L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the establishment of cell polarity in epithelial cells. Each L27_N domain consists of three alpha-helices, the first two of which form an antiparallel coiled-coil. Two L27 domains come together to form a four-helical bundle with the antiparallel coiled-coils formed by the first two helices. The third helix of each domain forms another coiled-coil packing at one end of the four-helix bundle, creating a large hydrophobic interface: the hydrophobic interactions are the major force that drives heterodimer formation.


Pssm-ID: 462666  Cd Length: 48  Bit Score: 85.84  E-value: 7.74e-21
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370465470  89 EIEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNKDFQNAFKIHNAIT 136
Cdd:pfam09060   1 ELEELLQSLKHVQHCLTDSQSQQDVELILQLLQKEDFQNAFSIHNAVS 48
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 220-300 5.03e-12

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 62.01  E-value: 5.03e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  220 VKIVRIEKaRDIPLGATVRNEMDS---VIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTF 296
Cdd:smart00228   2 PRLVELEK-GGGGLGFSLVGGKDEgggVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTL 79


                   ....
gi 1370465470  297 VLIP 300
Cdd:smart00228  80 TVLR 83
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 315-375 5.65e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 57.93  E-value: 5.65e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370465470  315 HVKAHFDYDPSDDPyvpcrelGLSFQKGDILHVISQEDPNWWQAYREGDEdnqplAGLVPG 375
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRLGRGK-----EGLFPS 52
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 223-299 3.09e-10

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 56.91  E-value: 3.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 223 VRIEKARDIPLGATVR----NEMDSVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:pfam00595   2 VTLEKDGRGGLGFSLKggsdQGDPGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80


                  .
gi 1370465470 299 I 299
Cdd:pfam00595  81 L 81
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 315-377 7.83e-10

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 54.91  E-value: 7.83e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYdpsddpyVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVPGKS 377
Cdd:pfam07653   1 YGRVIFDY-------VGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRV------GLVPSTA 50
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 233-313 1.61e-09

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 59.88  E-value: 1.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 233 LGATVRNEMDSVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGtlTFVLIpsqQIKPPPAKET 312
Cdd:COG0793    62 LGAELGEEDGKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVAGLTLDDAVKLLRGKAG--TKVTL---TIKRPGEGEP 135


                  .
gi 1370465470 313 V 313
Cdd:COG0793   136 I 136
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
155-203 1.81e-07

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 47.89  E-value: 1.81e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370465470  155 LAQEVQTVLKP--VHHKEGQELTALLNTPHIQALLLAHDKVAEQEMQLEPI 203
Cdd:smart00569   2 RLLELLEELQSllSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLP 52
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
91-146 4.69e-06

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 44.04  E-value: 4.69e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470   91 EDLFSSLKHIQHTLvdsQSQEDISLLLQLVQNKDFQNAFKIHNAITVHMNKASPPF 146
Cdd:smart00569   1 QRLLELLEELQSLL---SPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 152-197 7.18e-06

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 43.57  E-value: 7.18e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1370465470 152 AQDLAQEVQTvlKPVHHKEGQELTALLNTPHIQALLLAHDKVAEQE 197
Cdd:pfam02828   4 VLELLEDLQP--LSEASEDLAELQKLLQSPHLQALLEAHDKVAQKV 47
degP_htrA_DO TIGR02037
periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various ...
 244-276 7.60e-03

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 273938 [Multi-domain]  Cd Length: 428  Bit Score: 39.13  E-value: 7.60e-03
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1370465470 244 VIISRIVKGGAAEKSGlLHEGDEVLEINGIEIR 276
Cdd:TIGR02037 259 ALVAQVLPGSPAEKAG-LKAGDVITSVNGKPIS 290
 
Name Accession Description Interval E-value
GuKc smart00072
Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to ...
 457-627 1.96e-50

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.


Pssm-ID: 214504 [Multi-domain]  Cd Length: 174  Bit Score: 172.48  E-value: 1.96e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  457 GQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSG 536
Cdd:smart00072   4 GKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVAEKG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  537 KICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKnPKPEELREIIEKTREMEQNNgHYFDTAIVNSDLDK 616
Cdd:smart00072  84 KHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQRGT-ETSERIQKRLAAAQKEAQEY-HLFDYVIVNDDLED 161

                          170
                   ....*....|.
gi 1370465470  617 AYQELLRLINK 627
Cdd:smart00072 162 AYEELKEILEA 172
PDZ_MPP5-like cd06798
PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related ...
 221-300 2.34e-49

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467259 [Multi-domain]  Cd Length: 79  Bit Score: 166.37  E-value: 2.34e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDiPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06798     1 KIVRIEKTRE-PLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLIP 79
Guanylate_kin pfam00625
Guanylate kinase;
444-628 3.16e-49

Guanylate kinase;


Pssm-ID: 395500  Cd Length: 182  Bit Score: 169.87  E-value: 3.16e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 444 RKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYG 523
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 524 TSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKnpkpEELREIIEKTREMEQNNGH 603
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKGRGK----EQEEKINKRMAAAEQEFQH 156

                         170       180
                  ....*....|....*....|....*.
gi 1370465470 604 Y-FDTAIVNSDLDKAYQELLRLINKL 628
Cdd:pfam00625 157 YeFDVIIVNDDLEEAYKKLKEALEAE 182
guanyl_kin TIGR03263
guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP ...
 446-627 1.83e-42

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]


Pssm-ID: 213788  Cd Length: 179  Bit Score: 151.11  E-value: 1.83e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 446 RPIILIGPQNCGQNELRQRLMnKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTS 525
Cdd:TIGR03263   1 LLIVISGPSGAGKSTLVKALL-EEDPNLKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 526 IDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNpKPEELREIIEKTR-EMEQnnGHY 604
Cdd:TIGR03263  80 KSPVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILPPSLEELERRLRKRGTD-SEEVIERRLAKAKkEIAH--ADE 156

                         170       180
                  ....*....|....*....|...
gi 1370465470 605 FDTAIVNSDLDKAYQELLRLINK 627
Cdd:TIGR03263 157 FDYVIVNDDLEKAVEELKSIILA 179
SH3_MPP5 cd12036
Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); ...
 315-377 2.70e-42

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212969  Cd Length: 63  Bit Score: 146.40  E-value: 2.70e-42
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd12036     1 HVRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAYREGEEDNQSLAGLIPSKS 63
GMPK cd00071
Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), ...
 447-622 4.02e-38

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.


Pssm-ID: 238026  Cd Length: 137  Bit Score: 137.66  E-value: 4.02e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 447 PIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSI 526
Cdd:cd00071     1 LIVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 527 DSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPsqerlrallakegknpkpeelreiiektremeqnnghyfD 606
Cdd:cd00071    81 AAVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP---------------------------------------D 121

                         170
                  ....*....|....*.
gi 1370465470 607 TAIVNSDLDKAYQELL 622
Cdd:cd00071   122 YVIVNDDLEKAYEELK 137
PLN02772 PLN02772
guanylate kinase
 443-625 3.57e-35

guanylate kinase


Pssm-ID: 215414 [Multi-domain]  Cd Length: 398  Bit Score: 137.28  E-value: 3.57e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 443 NRKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLY 522
Cdd:PLN02772  133 NAEKPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLY 212

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 523 GTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNPKPEELREIIEKTREMEQNNG 602
Cdd:PLN02772  213 GTSIEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRARGTETEEQIQKRLRNAEAELEQGKS 292

                         170       180
                  ....*....|....*....|....
gi 1370465470 603 HY-FDTAIVNSDLDKAYQELLRLI 625
Cdd:PLN02772  293 SGiFDHILYNDNLEECYKNLKKLL 316
PDZ_MPP-like cd06726
PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 ...
 221-300 5.26e-35

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467208 [Multi-domain]  Cd Length: 80  Bit Score: 127.00  E-value: 5.26e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDIPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06726     1 RLVEFEKARDEPLGATIKMEEDSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKLIP 80
gmk PRK00300
guanylate kinase; Provisional
 441-625 1.78e-33

guanylate kinase; Provisional


Pssm-ID: 234719  Cd Length: 205  Bit Score: 127.13  E-value: 1.78e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 441 PANRKRPIILIGPQNCGQNELRQRLMnKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKN 520
Cdd:PRK00300    1 MMRRGLLIVLSGPSGAGKSTLVKALL-ERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 521 LYGTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGknpkpEELREIIEKtR----- 595
Cdd:PRK00300   80 YYGTPRSPVEEALAAGKDVLLEIDWQGARQVKKKMPDAVSIFILPPSLEELERRLRGRG-----TDSEEVIAR-Rlakar 153

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1370465470 596 -EMEqnngHY--FDTAIVNSDLDKAYQELLRLI 625
Cdd:PRK00300  154 eEIA----HAseYDYVIVNDDLDTALEELKAII 182
Gmk COG0194
Guanylate kinase [Nucleotide transport and metabolism];
448-633 5.81e-33

Guanylate kinase [Nucleotide transport and metabolism];


Pssm-ID: 439964  Cd Length: 190  Bit Score: 125.18  E-value: 5.81e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 448 IILIGPQNCGQNELRQRLMnKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSID 527
Cdd:COG0194     5 IVLSGPSGAGKTTLVKALL-ERDPDLRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 528 SVRQVINSGKICLLSLRTQSLKTLRNSdLKPYI-IFIAPPSQERLRALLAKEGknpkpEELREIIEK-----TREMEQnn 601
Cdd:COG0194    84 EVEEALAAGKDVLLEIDVQGARQVKKK-FPDAVsIFILPPSLEELERRLRGRG-----TDSEEVIERrlakaREELAH-- 155

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1370465470 602 GHYFDTAIVNSDLDKAYQELLRLI--NKLDTEPQ 633
Cdd:COG0194   156 ADEFDYVVVNDDLDRAVEELKAIIraERLRRERQ 189
SH3_MPP cd11862
Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) ...
 315-376 9.63e-32

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212796  Cd Length: 61  Bit Score: 117.30  E-value: 9.63e-32
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGdeDNQPLAGLVPGK 376
Cdd:cd11862     1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVG--DPNGRAGLIPSQ 60
PDZ_MPP3-MPP4-MPP7-like cd06799
PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; ...
 221-300 8.84e-25

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467260 [Multi-domain]  Cd Length: 81  Bit Score: 98.08  E-value: 8.84e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDiPLGATV-RNEMD-SVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd06799     1 KIVRLVKNNE-PLGATIkRDEKTgAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKL 79


                  ..
gi 1370465470 299 IP 300
Cdd:cd06799    80 IP 81
gmk PRK14738
guanylate kinase; Provisional
 442-625 1.02e-23

guanylate kinase; Provisional


Pssm-ID: 237809  Cd Length: 206  Bit Score: 99.42  E-value: 1.02e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 442 ANRKRPIILIGPQNCGQNELRQRlMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNL 521
Cdd:PRK14738   10 PAKPLLVVISGPSGVGKDAVLAR-MRERKLPFHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 522 YGTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEgKNPKPEEL-REIIEKTREMEQN 600
Cdd:PRK14738   89 YGVPKAPVRQALASGRDVIVKVDVQGAASIKRLVPEAVFIFLAPPSMDELTRRLELR-RTESPEELeRRLATAPLELEQL 167

                         170       180
                  ....*....|....*....|....*..
gi 1370465470 601 NGhyFDTAIVN--SDLDKAYQELLRLI 625
Cdd:PRK14738  168 PE--FDYVVVNpeDRLDEAVAQIMAII 192
SH3_MPP7 cd12033
Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); ...
 316-376 6.02e-23

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212966  Cd Length: 61  Bit Score: 92.39  E-value: 6.02e-23
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDnqPLAGLVPGK 376
Cdd:cd12033     2 IKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDAN--PRAGLIPSK 60
L27_N pfam09060
L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the ...
 89-136 7.74e-21

L27_N; The L27_N domain plays a role in the biogenesis of tight junctions and in the establishment of cell polarity in epithelial cells. Each L27_N domain consists of three alpha-helices, the first two of which form an antiparallel coiled-coil. Two L27 domains come together to form a four-helical bundle with the antiparallel coiled-coils formed by the first two helices. The third helix of each domain forms another coiled-coil packing at one end of the four-helix bundle, creating a large hydrophobic interface: the hydrophobic interactions are the major force that drives heterodimer formation.


Pssm-ID: 462666  Cd Length: 48  Bit Score: 85.84  E-value: 7.74e-21
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370465470  89 EIEDLFSSLKHIQHTLVDSQSQEDISLLLQLVQNKDFQNAFKIHNAIT 136
Cdd:pfam09060   1 ELEELLQSLKHVQHCLTDSQSQQDVELILQLLQKEDFQNAFSIHNAVS 48
SH3_MPP3 cd12039
Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); ...
 316-378 2.82e-20

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212972  Cd Length: 62  Bit Score: 84.62  E-value: 2.82e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQplAGLVPGKSF 378
Cdd:cd12039     2 MRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLR--AGLIPSKQF 62
SH3_MPP2 cd12037
Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); ...
 316-376 8.51e-20

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212970  Cd Length: 59  Bit Score: 83.46  E-value: 8.51e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQA-YREGDEdnqplAGLVPGK 376
Cdd:cd12037     2 VKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQAcHVEGGS-----AGLIPSQ 58
SH3_MPP1-like cd12035
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1) ...
 315-374 4.25e-19

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212968  Cd Length: 62  Bit Score: 81.32  E-value: 4.25e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGdeDNQPLAGLVP 374
Cdd:cd12035     1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQARKPG--ASKEPAGLIP 58
SH3_MPP1 cd12080
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); ...
 315-374 9.25e-19

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213013  Cd Length: 62  Bit Score: 80.38  E-value: 9.25e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQplAGLVP 374
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEES--AGLIP 58
SH3_MPP6 cd12038
Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); ...
 316-376 4.69e-18

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212971  Cd Length: 61  Bit Score: 78.57  E-value: 4.69e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQA--YREGDEdnqplAGLVPGK 376
Cdd:cd12038     2 VKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQAshVKEGGS-----AGLIPSQ 59
SH3_DLG-like cd11861
Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding ...
 315-377 1.03e-17

Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding proteins that cluster at synapses and are also called PSD (postsynaptic density)-95 proteins or SAPs (synapse-associated proteins). They play important roles in synaptic development and plasticity, cell polarity, migration and proliferation. They are members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG-like proteins contain three PDZ domains and varying N-terminal regions. All DLG proteins exist as alternatively-spliced isoforms. Vertebrates contain four DLG proteins from different genes, called DLG1-4. DLG4 and DLG2 are found predominantly at postsynaptic sites and they mediate surface ion channel and receptor clustering. DLG3 is found axons and some presynaptic terminals. DLG1 interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212795 [Multi-domain]  Cd Length: 61  Bit Score: 77.36  E-value: 1.03e-17
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRelGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd11861     1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVTPNGEEEEVGVIPSKR 61
SH3_CASK cd12081
Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a ...
 315-374 1.39e-17

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213014  Cd Length: 62  Bit Score: 77.25  E-value: 1.39e-17
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQplAGLVP 374
Cdd:cd12081     1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGT--AGLIP 58
gmk PRK14737
guanylate kinase; Provisional
 457-625 2.53e-17

guanylate kinase; Provisional


Pssm-ID: 173199  Cd Length: 186  Bit Score: 80.42  E-value: 2.53e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 457 GQNELRQRLMNKEKDrFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSG 536
Cdd:PRK14737   16 GKSTIIQALLEEHPD-FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTPKAFIEDAFKEG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 537 KICLLSLRTQSLKTLRnsDLKP---YIIFIAPPSQERLRALLAKEGKNPKPEELREIIEKTREMEQNNGhyFDTAIVNSD 613
Cdd:PRK14737   95 RSAIMDIDVQGAKIIK--EKFPeriVTIFIEPPSEEEWEERLIHRGTDSEESIEKRIENGIIELDEANE--FDYKIINDD 170

                         170
                  ....*....|..
gi 1370465470 614 LDKAYQELLRLI 625
Cdd:PRK14737  171 LEDAIADLEAII 182
PDZ_Par6-like cd06718
PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F ...
 221-291 3.27e-15

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467202 [Multi-domain]  Cd Length: 84  Bit Score: 71.06  E-value: 3.27e-15
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470 221 KIVRIEKARDIPLGATVR--NEMD---SVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMH 291
Cdd:cd06718     1 RRVELIKPPGKPLGFYIRdgNGVErvpGIFISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMVAPT 76
PDZ_MPP1-like cd10830
PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 ...
 221-300 2.71e-14

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467266 [Multi-domain]  Cd Length: 81  Bit Score: 68.35  E-value: 2.71e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDIPLGATVR-NEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLI 299
Cdd:cd10830     1 RLVQFEKNTEEPMGITLKlNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80


                  .
gi 1370465470 300 P 300
Cdd:cd10830    81 P 81
PDZ_MPP6-MPP2-like cd10832
PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 ...
 221-300 3.60e-14

PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP6, MPP2, and related domains. MPP6 (also known as MAGUK p55 subfamily member, Protein associated with Lin-7, 2 (PALS2), Veli-associated MAGUK 1, and VAM-1) is a membrane-associated guanylate kinase (MAGUK)-like protein. MPP6 is a regulator of Lin-7 expression and localization. MPP6 is also known to bind cell-adhesion protein, nectin-like molecule-2 (Necl-2), and localize to the basolateral plasma membrane in mammalian epithelial cells. MPP2 (also known as MAGUK p55 subfamily member 2) is a postsynaptic protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Other members of this family include the Drosophila Vari protein, an essential basolateral septate junction protein which interacts with the cell-adhesion protein neurexin IV. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467268 [Multi-domain]  Cd Length: 78  Bit Score: 68.02  E-value: 3.60e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDIPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDvnEVFDLLSDMHGTLTFVLIP 300
Cdd:cd10832     1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGSPE--QLQEMLKNASGSVTLKILP 78
SH3_MPP4 cd12034
Src Homology 3 domain of Membrane Protein, Palmitoylated 4 (or MAGUK p55 subfamily member 4); ...
 315-374 6.38e-14

Src Homology 3 domain of Membrane Protein, Palmitoylated 4 (or MAGUK p55 subfamily member 4); MPP4, also called Disks Large homolog 6 (DLG6) or Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 5 protein (ALS2CR5), is a retina-specific scaffolding protein that plays a role in organizing presynaptic protein complexes in the photoreceptor synapse, where it localizes to the plasma membrane. It is required in the proper localization of calcium ATPases and for maintenance of calcium homeostasis. MPP4 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212967  Cd Length: 61  Bit Score: 66.46  E-value: 6.38e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 315 HVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNqpLAGLVP 374
Cdd:cd12034     1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSDLAA--CAGLIP 58
PDZ_CASK-like cd10831
PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related ...
 221-300 1.36e-13

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467267 [Multi-domain]  Cd Length: 81  Bit Score: 66.35  E-value: 1.36e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 221 KIVRIEKARDIPLGATVR-NEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLI 299
Cdd:cd10831     1 RLVQFQKNTDEPMGITLKmNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIV 80


                  .
gi 1370465470 300 P 300
Cdd:cd10831    81 P 81
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 223-298 7.34e-13

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467153 [Multi-domain]  Cd Length: 81  Bit Score: 64.10  E-value: 7.34e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370465470 223 VRIEKARDIPLGATVR---NEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd00136     2 VTLEKDPGGGLGFSIRggkDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 220-300 5.03e-12

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 62.01  E-value: 5.03e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470  220 VKIVRIEKaRDIPLGATVRNEMDS---VIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTF 296
Cdd:smart00228   2 PRLVELEK-GGGGLGFSLVGGKDEgggVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTL 79


                   ....
gi 1370465470  297 VLIP 300
Cdd:smart00228  80 TVLR 83
SH3_DLG2 cd12032
Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 ...
 314-383 3.18e-11

Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 (PSD93) or Channel-associated protein of synapse-110 (chapsyn 110), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. The DLG2 delta isoform binds inwardly rectifying potassium Kir2 channels, which determine resting membrane potential in neurons. It regulates the spatial and temporal distribution of Kir2 channels within neuronal membranes. DLG2 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG2 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212965  Cd Length: 74  Bit Score: 59.32  E-value: 3.18e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 314 IHVKAHFDYDPSDDPYVPCRelGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKSFQQQRE 383
Cdd:cd12032     6 LYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARRVTPDGDSEEMGVIPSKRRVERKE 73
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 315-375 5.65e-11

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 57.93  E-value: 5.65e-11
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370465470  315 HVKAHFDYDPSDDPyvpcrelGLSFQKGDILHVISQEDPNWWQAYREGDEdnqplAGLVPG 375
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRLGRGK-----EGLFPS 52
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 223-299 3.09e-10

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 56.91  E-value: 3.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 223 VRIEKARDIPLGATVR----NEMDSVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:pfam00595   2 VTLEKDGRGGLGFSLKggsdQGDPGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80


                  .
gi 1370465470 299 I 299
Cdd:pfam00595  81 L 81
SH3_DLG3 cd12029
Src Homology 3 domain of Disks Large homolog 3; DLG3, also called synapse-associated protein ...
 314-376 6.68e-10

Src Homology 3 domain of Disks Large homolog 3; DLG3, also called synapse-associated protein 102 (SAP102), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. Mutations in DLG3 cause midgestational embryonic lethality in mice and may be associated with nonsyndromic X-linked mental retardation in humans. It interacts with the NEDD4 (neural precursor cell-expressed developmentally downregulated 4) family of ubiquitin ligases and promotes apical tight junction formation. DLG3 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG3 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212962  Cd Length: 67  Bit Score: 55.48  E-value: 6.68e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 314 IHVKAHFDYDPSDDPYVPCRelGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGK 376
Cdd:cd12029     3 LYVRALFDYDRTRDSCLPSQ--GLSFSYGDILHVINASDDEWWQARLVTPHGESEQIGVIPSK 63
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 315-377 7.83e-10

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 54.91  E-value: 7.83e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 315 HVKAHFDYdpsddpyVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVPGKS 377
Cdd:pfam07653   1 YGRVIFDY-------VGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRV------GLVPSTA 50
SH3_DLG1 cd12031
Src Homology 3 domain of Disks Large homolog 1; DLG1, also called synapse-associated protein ...
 314-376 1.04e-09

Src Homology 3 domain of Disks Large homolog 1; DLG1, also called synapse-associated protein 97 (SAP97), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. DLG1 plays roles in regulating cell polarity, proliferation, migration, and cycle progression. It interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. It also interacts with PKCalpha and promotes wound healing. DLG1 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG1 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212964  Cd Length: 67  Bit Score: 55.08  E-value: 1.04e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370465470 314 IHVKAHFDYDPSDDPYVPCRelGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGK 376
Cdd:cd12031     3 LYVRALFDYDKTKDSGLPSQ--GLNFKFGDILHVVNASDDEWWQARQVTADGESEEIGVIPSK 63
PDZ6_GRIP1-2-like cd06683
PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 232-295 1.54e-09

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467171 [Multi-domain]  Cd Length: 85  Bit Score: 55.00  E-value: 1.54e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370465470 232 PLGATV---RNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLT 295
Cdd:cd06683    14 PLGITIsgtEEPFDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNAGDTVT 80
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 315-374 1.57e-09

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 53.62  E-value: 1.57e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 315 HVKAHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGDEdnqplAGLVP 374
Cdd:cd00174     1 YARALYDYEAQDD-----DEL--SFKKGDIITVLEKDDDGWWEGELNGGR-----EGLFP 48
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 233-313 1.61e-09

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 59.88  E-value: 1.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 233 LGATVRNEMDSVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGtlTFVLIpsqQIKPPPAKET 312
Cdd:COG0793    62 LGAELGEEDGKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVAGLTLDDAVKLLRGKAG--TKVTL---TIKRPGEGEP 135


                  .
gi 1370465470 313 V 313
Cdd:COG0793   136 I 136
PDZ2_Scribble-like cd06703
PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 238-298 2.81e-09

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467187 [Multi-domain]  Cd Length: 92  Bit Score: 54.57  E-value: 2.81e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370465470 238 RNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd06703    28 RDGDEGIFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSPTITLVV 88
cpPDZ_CPP-like cd06782
circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, ...
 233-287 4.14e-09

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467623 [Multi-domain]  Cd Length: 88  Bit Score: 53.64  E-value: 4.14e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470 233 LGATVR-NEMDSVIISRIVKGGAAEKSGLLhEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06782     4 IGIEIGkDDDGYLVVVSPIPGGPAEKAGIK-PGDVIVAVDGESVRGMSLDEVVKLL 58
PDZ_syntrophin-like cd06801
PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 244-276 1.51e-08

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467262 [Multi-domain]  Cd Length: 83  Bit Score: 52.19  E-value: 1.51e-08
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIR 276
Cdd:cd06801    27 ILISKIFKGQAADQTGQLFVGDAILSVNGENLE 59
PDZ7_PDZD2-PDZ4_hPro-IL-16-like cd06763
PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 ...
 244-277 1.80e-08

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467244 [Multi-domain]  Cd Length: 86  Bit Score: 51.85  E-value: 1.80e-08
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06763    30 LTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQG 63
SH3_DLG4 cd12030
Src Homology 3 domain of Disks Large homolog 4; DLG4, also called postsynaptic density-95 ...
 315-376 3.27e-08

Src Homology 3 domain of Disks Large homolog 4; DLG4, also called postsynaptic density-95 (PSD95) or synapse-associated protein 90 (SAP90), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. It is responsible for the membrane clustering and retention of many transporters and receptors such as potassium channels and PMCA4b, a P-type ion transport ATPase, among others. DLG4 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG4 contains three PDZ domains. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212963  Cd Length: 66  Bit Score: 50.70  E-value: 3.27e-08
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gi 1370465470 315 HVKAHFDYDPSDDpyvpCREL--GLSFQKGDILHVISQEDPNWWQAYR-----EGDEdnqplAGLVPGK 376
Cdd:cd12030     3 YIRALFDYDKTKD----CGFLsqALSFRFGDVLHVIDAGDEEWWQARRvhsdsETEE-----IGFIPSK 62
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
 316-357 3.41e-08

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 50.18  E-value: 3.41e-08
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gi 1370465470 316 VKAHFDYDPsDDPYvpcrelGLSFQKGDILHVISQEDPNWWQ 357
Cdd:cd11951     2 VQAQYDFSA-EDPS------QLSFRRGDIIEVLDCPDPNWWR 36
PDZ3_MAGI-1_3-like cd06733
PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 243-287 1.28e-07

PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467215 [Multi-domain]  Cd Length: 85  Bit Score: 49.53  E-value: 1.28e-07
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gi 1370465470 243 SVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06733    26 QVSIGAIVPGGAADLDGRLRTGDELLSVDGVNVVGASHHKVVDLM 70
PDZ_RIM-like cd06714
PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ ...
 245-292 1.80e-07

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467198 [Multi-domain]  Cd Length: 95  Bit Score: 49.47  E-value: 1.80e-07
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gi 1370465470 245 IISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHG 292
Cdd:cd06714    41 YVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQDIISQSKG 88
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
155-203 1.81e-07

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 47.89  E-value: 1.81e-07
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gi 1370465470  155 LAQEVQTVLKP--VHHKEGQELTALLNTPHIQALLLAHDKVAEQEMQLEPI 203
Cdd:smart00569   2 RLLELLEELQSllSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLP 52
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
 316-375 2.06e-07

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 48.06  E-value: 2.06e-07
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gi 1370465470 316 VKAHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVPG 375
Cdd:cd11772     2 FRALYDYEAQHP-----DEL--SFEEGDLLYISDKSDPNWWKATCGGKT------GLIPS 48
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
 316-357 2.18e-07

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 47.91  E-value: 2.18e-07
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gi 1370465470 316 VKAHFDYDPSDDpyvpcRELGlsFQKGDILHVISQEDPNWWQ 357
Cdd:cd11949     2 VQALFDFDPQED-----GELG--FRRGDFIEVMDNSDPNWWK 36
PDZ_Lin-7-like cd06796
PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 240-297 3.91e-07

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467258 [Multi-domain]  Cd Length: 86  Bit Score: 48.20  E-value: 3.91e-07
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gi 1370465470 240 EMDSVI-ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFV 297
Cdd:cd06796    23 EQNSPIyISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLV 81
PDZ2_DLG5-like cd06765
PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 244-288 4.67e-07

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467246 [Multi-domain]  Cd Length: 77  Bit Score: 47.73  E-value: 4.67e-07
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLS 288
Cdd:cd06765    18 VFISRIVPGSPAAKEGSLTVGDRIIAINGIALDNKSLSECEALLR 62
PDZ1_APBA1_3-like cd06720
PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, ...
 221-277 7.01e-07

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,2,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467203 [Multi-domain]  Cd Length: 86  Bit Score: 47.25  E-value: 7.01e-07
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gi 1370465470 221 KIVRIEKARDIPLGATV----RNEM-DSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06720     1 KEVVVEKQKGEILGVVIvesgWGSLlPTVVVANMMPGGPAARSGKLNIGDQIMSINGTSLVG 62
PDZ2-PTPN13_FRMPD2-like cd06792
PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and ...
 249-298 1.06e-06

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467254 [Multi-domain]  Cd Length: 87  Bit Score: 46.82  E-value: 1.06e-06
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gi 1370465470 249 IVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd06792    36 LVPGGAAEQDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQVVTLVL 85
PDZ2_Par3-like cd23058
PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 229-298 1.15e-06

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467271 [Multi-domain]  Cd Length: 93  Bit Score: 46.87  E-value: 1.15e-06
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gi 1370465470 229 RDIPLGATvrnemDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL--SDMHGTLTFVL 298
Cdd:cd23058    24 RDNPTGGS-----GPIYIKNILPKGAAIQDGRLKAGDRLLEVNGVDVTGKTQEEVVSLLrsTKLGGTVSLVV 90
PDZ_SNX27-like cd23070
PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density ...
 246-300 1.24e-06

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467283 [Multi-domain]  Cd Length: 93  Bit Score: 47.02  E-value: 1.24e-06
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gi 1370465470 246 ISRIVKGGAAEKSGLLhEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd23070    40 VSAVLEGGAADKAGVR-KGDRILEVNGVNVEGATHKQVVDLIKSGGDELTLTVIS 93
PDZ4_MAGI-1_3-like cd06734
PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 246-300 1.35e-06

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467216 [Multi-domain]  Cd Length: 84  Bit Score: 46.45  E-value: 1.35e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06734    30 IGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIVP 84
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 317-374 1.36e-06

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 45.27  E-value: 1.36e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370465470 317 KAHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGDEDnqplaGLVP 374
Cdd:pfam00018   1 VALYDYTAQEP-----DEL--SFKKGDIIIVLEKSEDGWWKGRNKGGKE-----GLIP 46
PDZ4_GRIP1-2-like cd06686
PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 245-289 2.06e-06

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467174 [Multi-domain]  Cd Length: 99  Bit Score: 46.57  E-value: 2.06e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1370465470 245 IISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSD 289
Cdd:cd06686    39 LISFIEPDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLRD 83
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
 328-357 2.23e-06

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 45.10  E-value: 2.23e-06
                          10        20        30
                  ....*....|....*....|....*....|
gi 1370465470 328 PYVPCRELGLSFQKGDILHVISQEDPNWWQ 357
Cdd:cd11840     7 PYTAQNEDELSFQKGDIINVLSKDDPDWWR 36
SH3_ZO cd11859
Src homology 3 domain of the Tight junction proteins, Zonula occludens (ZO) proteins; ZO ...
 315-377 2.56e-06

Src homology 3 domain of the Tight junction proteins, Zonula occludens (ZO) proteins; ZO proteins are scaffolding proteins that associate with each other and with other proteins of the tight junction, zonula adherens, and gap junctions. They play roles in regulating cytoskeletal dynamics at these cell junctions. They are considered members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. Vertebrates contain three ZO proteins (ZO-1, ZO-2, and ZO-3) with redundant and non-redundant roles. They contain three PDZ domains, followed by SH3 and GuK domains; in addition, ZO-1 and ZO-2 contains a proline-rich (PR) actin binding domain at the C-terminus while ZO-3 contains this PR domain between the second and third PDZ domains. The C-terminal regions of the three ZO proteins are unique. The SH3 domain of ZO-1 has been shown to bind ZONAB, ZAK, afadin, and Galpha12. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212793  Cd Length: 62  Bit Score: 44.97  E-value: 2.56e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470 315 HVKAHFDYDPSDDpyvpcreLGLSFQKGDILHVIS---QEDPNWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd11859     1 YIRTHFDYEKPAK-------GELSFKKGEVFHVVDtlyQGTVGSWQAVRVGRNHQELERGVIPNKS 59
PDZ1_PTPN13_FRMPD2-like cd06694
PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ ...
 222-307 2.74e-06

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467180 [Multi-domain]  Cd Length: 92  Bit Score: 45.85  E-value: 2.74e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 222 IVRIEKARDIPLGATV-----RNEMDSVI-ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLT 295
Cdd:cd06694     4 IVTLKKDPQKGLGFTIvggenSGSLDLGIfVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPDKVE 83

                          90
                  ....*....|..
gi 1370465470 296 FVLipsQQIKPP 307
Cdd:cd06694    84 LII---SQPKSV 92
PDZ11_MUPP1-PDZ9_PATJ-like cd06674
PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ ...
 244-295 3.16e-06

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 11 of MUPP1, PDZ domain 9 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ11 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467162 [Multi-domain]  Cd Length: 87  Bit Score: 45.74  E-value: 3.16e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLT 295
Cdd:cd06674    29 VFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEAAAALLKCAQGKVR 80
PDZ3_GRIP1-2-like cd06684
PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 222-287 3.77e-06

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467172 [Multi-domain]  Cd Length: 87  Bit Score: 45.32  E-value: 3.77e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 222 IVRIEKARDIPLGATVRNEM----DSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06684     4 LVEIEKTPGSSLGITLSTSThrnkQVIVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLL 73
L27 smart00569
domain in receptor targeting proteins Lin-2 and Lin-7;
91-146 4.69e-06

domain in receptor targeting proteins Lin-2 and Lin-7;


Pssm-ID: 197794  Cd Length: 53  Bit Score: 44.04  E-value: 4.69e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470   91 EDLFSSLKHIQHTLvdsQSQEDISLLLQLVQNKDFQNAFKIHNAITVHMNKASPPF 146
Cdd:smart00569   1 QRLLELLEELQSLL---SPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53
PDZ3_harmonin cd06739
PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic ...
 219-272 4.88e-06

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467221 [Multi-domain]  Cd Length: 94  Bit Score: 45.38  E-value: 4.88e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370465470 219 TVKIVRIEKarDIPLGATVRNEMDS-----VIISRIVKGGAAEKSGLLHEGDEVLEING 272
Cdd:cd06739     2 QVRLLRIKK--NGPLDLALEGGIDSplggkIVVSAVYEGGAADKHGGIVKGDQIMMVNG 58
PDZ_6 pfam17820
PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.
 245-299 5.03e-06

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.


Pssm-ID: 436067 [Multi-domain]  Cd Length: 54  Bit Score: 44.06  E-value: 5.03e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370465470 245 IISRIVKGGAAEKSGLLhEGDEVLEINGIEIRgkDVNEVFDLLSDMHGTLTFVLI 299
Cdd:pfam17820   1 VVTAVVPGSPAERAGLR-VGDVILAVNGKPVR--SLEDVARLLQGSAGESVTLTV 52
L27 pfam02828
L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.
 152-197 7.18e-06

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.


Pssm-ID: 460717  Cd Length: 52  Bit Score: 43.57  E-value: 7.18e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1370465470 152 AQDLAQEVQTvlKPVHHKEGQELTALLNTPHIQALLLAHDKVAEQE 197
Cdd:pfam02828   4 VLELLEDLQP--LSEASEDLAELQKLLQSPHLQALLEAHDKVAQKV 47
PDZ2_L-delphilin-like cd06744
PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 ...
 222-287 8.97e-06

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467226 [Multi-domain]  Cd Length: 75  Bit Score: 43.80  E-value: 8.97e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370465470 222 IVRIEKArDIPLGATVRNEmDSVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06744     1 TVRVYRG-NGSFGFTLRGH-APVYIESVDPGSAAERAGL-KPGDRILFLNGLDVRNCSHDKVVSLL 63
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
 316-358 1.01e-05

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 43.12  E-value: 1.01e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1370465470 316 VKAHFDYDPSDDPYVPcrelglsFQKGDILHVISQEDPNWWQA 358
Cdd:cd11758     3 VRALFDFPGNDDEDLP-------FKKGEILTVIRKPEEQWWNA 38
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
 315-356 1.02e-05

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 43.04  E-value: 1.02e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1370465470 315 HVKAHFDYDPSDDPYvpcrelgLSFQKGDILHVISQEDPNWW 356
Cdd:cd11883     1 VVVALYDFTPKSKNQ-------LSFKAGDIIYVLNKDPSGWW 35
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
 316-374 1.03e-05

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 43.18  E-value: 1.03e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 316 VKAHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGD-EDNQPLAGLVP 374
Cdd:cd11773     2 YKALYDYEPQTE-----DEL--TIQEDDILYLLEKSDDDWWKVKLKVNsSDDDEPVGLVP 54
PDZ_nNOS-like cd06708
PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 ...
 223-275 1.17e-05

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This nNOS-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467192 [Multi-domain]  Cd Length: 110  Bit Score: 44.68  E-value: 1.17e-05
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gi 1370465470 223 VRIEKARDIPLGATVRNEMDS--VIISRIVKGGAAEKSGLLHEGDEVLEINGIEI 275
Cdd:cd06708     5 VRLFKRKVGGLGFLVKQRVCKppVIISDLIRGGAAEQSGLVQVGDIILAVNGRPL 59
PDZ_GOPC-like cd06800
PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and ...
 244-296 1.34e-05

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467261 [Multi-domain]  Cd Length: 83  Bit Score: 43.90  E-value: 1.34e-05
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTF 296
Cdd:cd06800    27 ILISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVTILSQQRGEITL 79
PDZ2_MUPP1-like cd06667
PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 244-297 1.38e-05

PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467155 [Multi-domain]  Cd Length: 80  Bit Score: 43.43  E-value: 1.38e-05
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFV 297
Cdd:cd06667    24 VVVKTILPGGVADRDGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCGSHVRLV 77
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
 337-374 1.81e-05

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 42.30  E-value: 1.81e-05
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gi 1370465470 337 LSFQKGDILHVISQEDPNWWQAYREGDEDNQplaGLVP 374
Cdd:cd11821    16 LTFSEGEIIVVTGEEDDEWWEGHIEGDPSRR---GVFP 50
PDZ1_GgSTXBP4-like cd06692
PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, ...
 244-277 1.96e-05

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467179 [Multi-domain]  Cd Length: 88  Bit Score: 43.36  E-value: 1.96e-05
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06692    28 IFIKRILPGGLAATDGRLKEGDLILEVNGESLQG 61
PDZ5_MAGI-1_3-like cd06735
PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 248-277 2.02e-05

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467217 [Multi-domain]  Cd Length: 84  Bit Score: 43.34  E-value: 2.02e-05
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gi 1370465470 248 RIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06735    32 RLAEDGPAQRDGRLRVGDQILEINGESTQG 61
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
 314-358 2.05e-05

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 42.18  E-value: 2.05e-05
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gi 1370465470 314 IHVkAHFDYDP--SDDpyvpcrelgLSFQKGDILHVISQEDPNWWQA 358
Cdd:cd11845     1 IYV-ALYDYEArtDDD---------LSFKKGDRLQILDDSDGDWWLA 37
COG3975 COG3975
Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];
233-283 2.17e-05

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];


Pssm-ID: 443174 [Multi-domain]  Cd Length: 591  Bit Score: 47.51  E-value: 2.17e-05
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gi 1370465470 233 LGATVRNEMDSVIISRIVKGGAAEKSGlLHEGDEVLEINGIEIRGKDVNEV 283
Cdd:COG3975   485 LGLRVSADGGGLVVTSVLWGSPAYKAG-LSAGDELLAIDGLRVTADNLDDA 534
PDZ1_Scribble-like cd06704
PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 242-297 2.54e-05

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467188 [Multi-domain]  Cd Length: 87  Bit Score: 43.04  E-value: 2.54e-05
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gi 1370465470 242 DSVIISRIVKGGAAEKSGlLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFV 297
Cdd:cd06704    30 EGIFISRVTEGGPAAKAG-VRVGDKLLEVNGVDLVDADHHEAVEALKNSGNTVTMV 84
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 315-356 2.63e-05

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 41.84  E-value: 2.63e-05
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gi 1370465470 315 HVKAHFDYDPSDDpyvpcrelG-LSFQKGDILHVISQEDPNWW 356
Cdd:cd11805     1 RVQALYDFNPQEP--------GeLEFRRGDIITVLDSSDPDWW 35
PDZ_shroom2_3_4-like cd06750
PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic ...
 232-298 2.75e-05

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467232 [Multi-domain]  Cd Length: 82  Bit Score: 42.71  E-value: 2.75e-05
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gi 1370465470 232 PLGATVRNEMDS---VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVnEVFDLLSDMHGTLTFVL 298
Cdd:cd06750    12 PWGFTLKGGLEHgepLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQ-EAIQLVKGSHKTLKLVV 80
PDZ_RGS12-like cd06710
PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 ...
 218-303 3.04e-05

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467194 [Multi-domain]  Cd Length: 76  Bit Score: 42.62  E-value: 3.04e-05
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gi 1370465470 218 ETVKIVRIEKArdipLGATVRNEMDSVIiSRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLsdmhGTLTFV 297
Cdd:cd06710     1 RTVEIARGRAG----YGFTISGQAPCVL-SCVVRGSPADVAGL-KAGDQILAVNGINVSKASHEDVVKLI----GKCTGV 70


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gi 1370465470 298 LIPSQQ 303
Cdd:cd06710    71 LRLVIA 76
PDZ2_PDZD2-like cd06758
PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 ...
 243-287 3.48e-05

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467239 [Multi-domain]  Cd Length: 88  Bit Score: 42.72  E-value: 3.48e-05
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gi 1370465470 243 SVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06758    30 GIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVAIL 74
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
 316-374 4.51e-05

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 41.30  E-value: 4.51e-05
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gi 1370465470 316 VKAHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVP 374
Cdd:cd11820     3 VRALYDFEAAED-----NEL--TFKAGEIITVLDDSDPNWWKGSNHRGE------GLFP 48
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 337-374 4.91e-05

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 41.19  E-value: 4.91e-05
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gi 1370465470 337 LSFQKGDILHVIS-QEDPNWWQAYREGDEdnqplaGLVP 374
Cdd:cd11804    16 LSFKKGSILKVLNmEDDPNWYKAELDGKE------GLIP 48
PDZ2-PDZRN4-like cd06716
PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related ...
 240-298 5.27e-05

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467200 [Multi-domain]  Cd Length: 88  Bit Score: 42.26  E-value: 5.27e-05
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gi 1370465470 240 EMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDvnEVFDLLSDMHGTLTFVL 298
Cdd:cd06716    29 EDTGIYVSEVDPNSIAAKDGRIREGDQILQINGVDVQNRE--EAIALLSEEEKSITLLV 85
PDZ4_Scribble-like cd06701
PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 223-298 5.51e-05

PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467185 [Multi-domain]  Cd Length: 98  Bit Score: 42.21  E-value: 5.51e-05
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gi 1370465470 223 VRIEKARDIPLGATVR-----------NEMDSVI-ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDM 290
Cdd:cd06701     7 LTIVKEPGEKLGISIRggakghagnplDPTDEGIfISKINPDGAAARDGRLKVGQRILEVNGQSLLGATHQEAVRILRSV 86


                  ....*...
gi 1370465470 291 HGTLTFVL 298
Cdd:cd06701    87 GDTLTLLV 94
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
 316-362 5.82e-05

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 41.21  E-value: 5.82e-05
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gi 1370465470 316 VKAHFDYDPSDdpyvpcrELGLSFQKGDILHVISQEDPNWWQAYREG 362
Cdd:cd12061     2 VRAKFNFQQTN-------EDELSFSKGDVIHVTRVEEGGWWEGTHNG 41
PDZ3_Scribble-like cd06702
PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 244-276 6.45e-05

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467186 [Multi-domain]  Cd Length: 89  Bit Score: 41.86  E-value: 6.45e-05
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gi 1370465470 244 VIISRIVKGGAAEKSGlLHEGDEVLEINGIEIR 276
Cdd:cd06702    34 IFISKVIPDGAAAKSG-LRIGDRILSVNGKDLR 65
PDZ10_MUPP1-PDZ8_PATJ-like cd06673
PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated ...
 230-277 6.79e-05

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467161 [Multi-domain]  Cd Length: 86  Bit Score: 41.89  E-value: 6.79e-05
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gi 1370465470 230 DIPLGAtvrnemdsVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06673    24 DTLLGA--------IIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRK 63
PDZ_SHANK1_3-like cd06746
PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and ...
 246-299 7.93e-05

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467228 [Multi-domain]  Cd Length: 101  Bit Score: 42.20  E-value: 7.93e-05
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gi 1370465470 246 ISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLI 299
Cdd:cd06746    46 LESVDPGGVADKAGL-KKGDFLLEINGEDVVKASHEQVVNLIRQSGNTLVLKVV 98
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
 316-374 8.36e-05

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 40.48  E-value: 8.36e-05
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gi 1370465470 316 VKAHFDYDPS-DDPYvpcrelGLSFQKGDILHVISQEDpNWWQAYREGDEdnqplAGLVP 374
Cdd:cd11855     2 ARALYPYDASpDDPN------ELSFEKGEILEVSDTSG-KWWQARKSNGE-----TGICP 49
PDZ_NHERF-like cd06768
PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related ...
 245-283 8.66e-05

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467249 [Multi-domain]  Cd Length: 80  Bit Score: 41.27  E-value: 8.66e-05
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gi 1370465470 245 IISRIVKGGAAEKSGLLhEGDEVLEINGIEIRGKDVNEV 283
Cdd:cd06768    26 FIREVDPGSPAERAGLK-DGDRLVEVNGENVEGESHEQV 63
PDZ8_MUPP1-PDZ7_PATJ-PDZ2_INAD-like cd06672
PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight ...
 238-299 9.17e-05

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ8 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467160 [Multi-domain]  Cd Length: 84  Bit Score: 41.51  E-value: 9.17e-05
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gi 1370465470 238 RNEMdSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLI 299
Cdd:cd06672    23 RSRM-SVFVVGIDPDGAAGKDGRIQVGDELLEINGQVLYGRSHLNASAIIKSAPSKVKIVFL 83
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
 316-362 9.26e-05

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 40.38  E-value: 9.26e-05
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gi 1370465470 316 VKAHFDYDPSDDPYvpcrelgLSFQKGDILHVISQEDPNWWQAYREG 362
Cdd:cd11877     2 VRAKFNFEGTNEDE-------LSFDKGDIITVTQVVEGGWWEGTLNG 41
PDZ4_LNX1_2-like cd06680
PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ ...
 243-300 1.09e-04

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467168 [Multi-domain]  Cd Length: 89  Bit Score: 41.18  E-value: 1.09e-04
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gi 1370465470 243 SVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIP 300
Cdd:cd06680    29 PFFVKSIVPGTPAYNDGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQRGRVTLTVVS 86
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
 337-374 1.57e-04

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 39.98  E-value: 1.57e-04
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gi 1370465470 337 LSFQKGDILHVI-SQEDPNWWQAYRE-GDEdnqplaGLVP 374
Cdd:cd11769    18 LPFKKGDILTIVaVTKDPNWYKAKNKdGRE------GMIP 51
PDZ3_PDZD2-PDZ1_hPro-IL-16-like cd06759
PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 ...
 246-277 1.83e-04

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467240 [Multi-domain]  Cd Length: 87  Bit Score: 40.72  E-value: 1.83e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06759    33 VKTIFPGGAAAEDGRLKEGDEILEVNGESLQG 64
SH3_CACNB1 cd12041
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta-1; The beta1 ...
 310-374 2.02e-04

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta-1; The beta1 subunit of voltage-dependent calcium channels (Ca(V)s) is one of four beta subunits present in vertebrates. It is the only beta subunit, as the beta1a variant, expressed in skeletal muscle; the beta1b variant is also widely expressed in other tissues including the heart and brain. Knockout of the beta1 gene in mice results in embryonic lethality, demonstrating its importance in development. Ca(V)s are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212974  Cd Length: 68  Bit Score: 39.96  E-value: 2.02e-04
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gi 1370465470 310 KETVIHVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWW--QAYREGDEdnqplAGLVP 374
Cdd:cd12041     1 KPVAFAVRTNVGYNPSPGDDVPVQGMAISFEPKDFLHIKEKYNNDWWigRLVKEGCE-----VGFIP 62
PDZ5_GRIP1-2-like cd06682
PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 223-287 2.15e-04

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467170 [Multi-domain]  Cd Length: 85  Bit Score: 40.41  E-value: 2.15e-04
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gi 1370465470 223 VRIEKARDIPLGATV-----RNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06682     3 VKLPKRSGVGLGITIsapknRKPGDPLIISDVKKGSVAHRTGTLEPGDKLLAIDNIRLDNCSMEDAAQIL 72
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
 337-374 2.72e-04

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 39.22  E-value: 2.72e-04
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gi 1370465470 337 LSFQKGDILHVISQEDPNWWQAYR-EGDEdnqplaGLVP 374
Cdd:cd11770    16 LSFKKGEVLRIISKRADGWWLAENsKGNR------GLVP 48
PDZ1_PDZD7-like cd10833
PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 220-273 2.89e-04

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467269 [Multi-domain]  Cd Length: 84  Bit Score: 40.11  E-value: 2.89e-04
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gi 1370465470 220 VKIVRIEKARDIPLGATVRNEMD---SVIISRIVKGGAAEKSGlLHEGDEVLEINGI 273
Cdd:cd10833     1 IHTVTVEKSPDGSLGFSVRGGSEhglGIFVSKVEEGSAAERAG-LCVGDKITEVNGV 56
DegQ COG0265
Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational ...
 244-291 2.94e-04

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440035 [Multi-domain]  Cd Length: 274  Bit Score: 43.21  E-value: 2.94e-04
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gi 1370465470 244 VIISRIVKGGAAEKSGLlHEGDEVLEINGIEIrgKDVNEVFDLLSDMH 291
Cdd:COG0265   203 VLVARVEPGSPAAKAGL-RPGDVILAVDGKPV--TSARDLQRLLASLK 247
PDZ_SYNJ2BP-like cd06709
PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 ...
 243-284 3.09e-04

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467193 [Multi-domain]  Cd Length: 86  Bit Score: 39.97  E-value: 3.09e-04
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gi 1370465470 243 SVIISRIVKGGAAEKSGLLHEGDEVLEING---IEIRGKDVNEVF 284
Cdd:cd06709    30 GIYVAKIKEDGAAAIDGRLQEGDKILEINGqslENLTHQDAVELF 74
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
 320-375 3.10e-04

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 38.89  E-value: 3.10e-04
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gi 1370465470 320 FDYDPSDDPyvpcrELGLSfqKGDILHVISQEDPNWWQAYREGdednqpLAGLVPG 375
Cdd:cd11824     6 YDYTAQEDD-----ELSIS--KGDVVAVIEKGEDGWWTVERNG------QKGLVPG 48
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
 316-357 3.29e-04

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 38.78  E-value: 3.29e-04
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gi 1370465470 316 VKAHFDYDPSDDPYvpcrelgLSFQKGDILHVISQEDPNWWQ 357
Cdd:cd11964     3 VRAIYDFEAAEDNE-------LTFKAGDIITILDDSDPNWWK 37
PDZ4_PDZD2-PDZ2_hPro-IL-16-like cd06760
PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 of human pro-interleukin-16 ...
 217-288 4.32e-04

PDZ domain 4 of PDZ domain containing 2 (PDZD2), PDZ domain 2 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the second PDZ domain (PDZ2) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467241 [Multi-domain]  Cd Length: 90  Bit Score: 39.56  E-value: 4.32e-04
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gi 1370465470 217 GETVKIVRIEKARDIPLGATV-----RNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLS 288
Cdd:cd06760     1 DRIIMEVTLNKEPGVGLGIGLcclplENDIPGIFIHHLSPGSVAHMDGRLRRGDQILEINGTSLRNVTLNEAYAILS 77
PDZ4_MUPP1-like cd06668
PDZ domain 4 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 246-290 5.16e-04

PDZ domain 4 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467156 [Multi-domain]  Cd Length: 88  Bit Score: 39.20  E-value: 5.16e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDM 290
Cdd:cd06668    34 IRSILPEGPVGRNGKLFSGDELLEVNGIQLLGLSHKEVVSILKEL 78
PDZ3_Par3-like cd23059
PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 246-287 5.35e-04

PDZ domain 3 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par-3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467272 [Multi-domain]  Cd Length: 103  Bit Score: 39.57  E-value: 5.35e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd23059    41 IKSIIHGGAASKDGRLRVNDQLIAVNGESLLGLTNSEAMETL 82
PDZ1_harmonin cd06737
PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 219-287 6.19e-04

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467219 [Multi-domain]  Cd Length: 85  Bit Score: 39.16  E-value: 6.19e-04
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gi 1370465470 219 TVKIVRIEKARDIPLGATVRNEMD---SVIISRIVKGGAAEKSGLlHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06737     1 KLRLVRLDRRGPESLGFSVRGGLEhgcGLFVSHVSPGSQADNKGL-RVGDEIVRINGYSISQCTHEEVINLI 71
SH3_9 pfam14604
Variant SH3 domain;
318-374 6.49e-04

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 37.98  E-value: 6.49e-04
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gi 1370465470 318 AHFDYDPSDDPYvpcrelgLSFQKGDILHVISQEDPNWWQAYREGdednqpLAGLVP 374
Cdd:pfam14604   1 ALYPYEPKDDDE-------LSLQRGDVITVIEESEDGWWEGINTG------RTGLVP 44
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
 329-374 7.11e-04

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 38.04  E-value: 7.11e-04
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gi 1370465470 329 YVPCRELGLSFQKGDILHVISQEDPNWWQAYREGdednqpLAGLVP 374
Cdd:cd11996     9 YTANNEDELSFSKGQLINVLNKDDPDWWQGEING------VTGLFP 48
PDZ3_Dlg1-2-4-like cd06795
PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 246-276 7.94e-04

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467257 [Multi-domain]  Cd Length: 91  Bit Score: 38.88  E-value: 7.94e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIR 276
Cdd:cd06795    29 ISFILAGGPADLSGELRRGDQILSVNGVDLR 59
SH3_SH3RF_2 cd11787
Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
 317-355 8.20e-04

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212721 [Multi-domain]  Cd Length: 53  Bit Score: 37.70  E-value: 8.20e-04
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gi 1370465470 317 KAHFDYDPSDDPYVPCrelgLSFQKGDILHVISQEDPNW 355
Cdd:cd11787     3 KALYDFEMKDEDEKDC----LTFKKGDVITVIRRVDENW 37
SH3_CACNB cd11863
Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta; ...
 316-356 8.34e-04

Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta; Voltage-dependent calcium channels (Ca(V)s) are multi-protein complexes that regulate the entry of calcium into cells. They impact muscle contraction, neuronal migration, hormone and neurotransmitter release, and the activation of calcium-dependent signaling pathways. They are composed of four subunits: alpha1, alpha2delta, beta, and gamma. The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants. All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212797 [Multi-domain]  Cd Length: 62  Bit Score: 38.03  E-value: 8.34e-04
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gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWW 356
Cdd:cd11863     3 VRTNVGYDGSLDDDSPVPGYAVSFEAKDFLHIKEKYNNDWW 43
PDZ6_PDZD2-PDZ3_hPro-IL-16-like cd06762
PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 ...
 240-287 8.84e-04

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the third PDZ domain (PDZ3) of human pro-interleukin-16 (isoform 1, also known as nPro-IL-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467243 [Multi-domain]  Cd Length: 86  Bit Score: 38.78  E-value: 8.84e-04
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gi 1370465470 240 EMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06762    25 ENKSITVHRVFPSGLAAQEGTIQKGDRILSINGKSLKGVTHGDALSVL 72
PDZ1_Par3-like cd06691
PDZ domain 1 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 246-278 9.01e-04

PDZ domain 1 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP) and related domains; Drosophila bazooka PDZ1 belongs to a different PDZ family. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include: Par-3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467178 [Multi-domain]  Cd Length: 98  Bit Score: 38.75  E-value: 9.01e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGK 278
Cdd:cd06691    37 IRGIEEGSRAERDGRFQENDCIVEINGVDLIDK 69
PDZ2_ZO1-like_ds cd06728
PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form ...
 246-298 9.61e-04

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467210 [Multi-domain]  Cd Length: 79  Bit Score: 38.36  E-value: 9.61e-04
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd06728    24 VKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVV 76
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
 317-374 9.91e-04

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 37.62  E-value: 9.91e-04
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gi 1370465470 317 KAHFDYDPSDDPyvpcrELGlsFQKGDILHVISQEDPNWWqayrEGDEDNQplAGLVP 374
Cdd:cd11803     4 RALYDFEPENEG-----ELG--FKEGDIITLTNQIDENWY----EGMVNGQ--SGFFP 48
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
 316-375 1.06e-03

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 37.30  E-value: 1.06e-03
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gi 1370465470 316 VKAHFDYDPSddpyvpcRELGLSFQKGDILHVISQEDPNWWQAYREGdednqpLAGLVPG 375
Cdd:cd11826     2 VVALYDYTAD-------KDDELSFQEGDIIYVTKKNDDGWYEGVLNG------VTGLFPG 48
SH3_Bem1p_1 cd11878
First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
 316-374 1.12e-03

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212811 [Multi-domain]  Cd Length: 54  Bit Score: 37.27  E-value: 1.12e-03
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gi 1370465470 316 VKAHFDYDPSDdpyvpcrELGLSFQKGDILHVISQEDPN-WWQAYregdednQPLA---GLVP 374
Cdd:cd11878     2 IRALYDYRAQT-------PGELSFSKGDFFHVIGEEDQGeWYEAT-------NPVTgkrGLVP 50
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
 316-363 1.34e-03

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 37.31  E-value: 1.34e-03
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gi 1370465470 316 VKAHFDYDPSDDPYvpcrelgLSFQKGDILHVISQEDPN-----WWQAYREGD 363
Cdd:cd11790     5 VRATHDYTAEDTDE-------LTFEKGDVILVIPFDDPEeqdegWLMGVKEST 50
SH3_RUSC2 cd11957
Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or ...
 337-374 1.43e-03

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212890  Cd Length: 52  Bit Score: 37.20  E-value: 1.43e-03
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gi 1370465470 337 LSFQKGDILHVISQEDPNWWQAYReGDEdnqplAGLVP 374
Cdd:cd11957    16 LSFNKGDILQVLSRADGDWLRCSL-GPD-----SGLVP 47
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
 318-376 1.44e-03

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 37.00  E-value: 1.44e-03
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gi 1370465470 318 AHFDYDPSDDpyvpcRELglSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVPGK 376
Cdd:cd11809     4 AQFDYTGRSE-----REL--SFKKGDSLTLYRQVSDDWWRGQLNGQD------GLVPHK 49
PDZ_AFDN-like cd06789
PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95) ...
 246-277 1.58e-03

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This AFDN family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467251 [Multi-domain]  Cd Length: 89  Bit Score: 38.04  E-value: 1.58e-03
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gi 1370465470 246 ISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06789    34 IKSVVKGGAADLDGRLQAGDQLLSVDGHSLVG 65
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
 337-374 1.60e-03

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 36.91  E-value: 1.60e-03
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gi 1370465470 337 LSFQKGDILHVISQ--EDPNWWQAyregdEDNQPLAGLVP 374
Cdd:cd11767    16 LSFEKGERLEIIEKpeDDPDWWKA-----RNALGTTGLVP 50
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
 315-362 1.69e-03

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 36.86  E-value: 1.69e-03
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gi 1370465470 315 HVKAHFDYDPSDDPYVPcrelglsFQKGDILHVISQEDPNWWQAYREG 362
Cdd:cd11995     2 QVIGMYDYTAQNDDELA-------FSKGQIINVLNKEDPDWWKGELNG 42
PDZ1_ZO1-like cd06727
PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ ...
 243-273 1.76e-03

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467209 [Multi-domain]  Cd Length: 87  Bit Score: 37.64  E-value: 1.76e-03
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gi 1370465470 243 SVIISRIVKGGAAEksGLLHEGDEVLEINGI 273
Cdd:cd06727    32 SIVISDVLKGGPAE--GKLQENDRVVSVNGV 60
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
 316-357 1.78e-03

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 36.87  E-value: 1.78e-03
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gi 1370465470 316 VKAHFDYDPSDDpyvpcrELGLSFQKGDILHVISQEDP-----NWWQ 357
Cdd:cd11771     2 CRALYDFTPENP------EMELSLKKGDIVAVLSKTDPlgrdsEWWK 42
SH3_ZO-3 cd12028
Src homology 3 domain of the Tight junction protein, Zonula occludens protein 3; ZO-3 is a ...
 315-377 1.80e-03

Src homology 3 domain of the Tight junction protein, Zonula occludens protein 3; ZO-3 is a scaffolding protein that associates with other ZO proteins and other proteins of the tight junction, zonula adherens, and gap junctions. ZO proteins play roles in regulating cytoskeletal dynamics at these cell junctions. ZO-3 is critical for epidermal barrier function. It regulates cyclin D1-dependent cell proliferation. It is considered a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. The C-terminal region of ZO-3 is the smallest of the three ZO proteins. The SH3 domain of the related protein ZO-1 has been shown to bind ZONAB, ZAK, afadin, and Galpha12. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212961  Cd Length: 65  Bit Score: 37.16  E-value: 1.80e-03
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gi 1370465470 315 HVKAHFDYDPsDDPyvpcreLGLSFQKGDILHVISQEDP---NWWQAYREGDEDNQPLAGLVPGKS 377
Cdd:cd12028     4 YIRTHFDYEP-DPP------SGLSFTRGEVFHVLDTMHRgklGSWLAVRMGRDLREMEKGIIPNQS 62
PDZ3_PTPN13_FRMPD2-like cd06695
PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ ...
 244-287 1.90e-03

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467181 [Multi-domain]  Cd Length: 90  Bit Score: 37.62  E-value: 1.90e-03
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06695    33 VRIKKLFPGQPAAESGLIQEGDVILAVNGEPLKGLSYQEVLSLL 76
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
 337-364 1.96e-03

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 36.59  E-value: 1.96e-03
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gi 1370465470 337 LSFQKGDILHVISQEDPNWWQAYREGDE 364
Cdd:cd11828    16 LGFKAGDVIEVLDMSDKDWWWGSIRDEE 43
SH3_RIM-BP cd11851
Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding ...
 316-375 2.07e-03

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212785  Cd Length: 62  Bit Score: 36.91  E-value: 2.07e-03
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gi 1370465470 316 VKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPnwwQAYREGdEDNQPLAGLVPG 375
Cdd:cd11851     2 MVALYDYNPETMSPNDDPEEELSFHAGDVVRVYGPMDE---DGFYYG-ELEGGRKGLVPS 57
PDZ_GIPC cd06707
PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and ...
 217-298 2.73e-03

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467191 [Multi-domain]  Cd Length: 89  Bit Score: 37.21  E-value: 2.73e-03
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gi 1370465470 217 GETvKIVRIEKARDIpLGATVR-NEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLT 295
Cdd:cd06707     2 GQP-KEIEVTKSEDA-LGLTITdNGAGYAFIKRIKEGSIMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKEIPIGET 79


                  ...
gi 1370465470 296 FVL 298
Cdd:cd06707    80 FTL 82
PDZ3_MUPP1-like cd06791
PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 234-287 2.75e-03

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467253 [Multi-domain]  Cd Length: 89  Bit Score: 37.21  E-value: 2.75e-03
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gi 1370465470 234 GATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06791    23 GEKASGELSGIFVKSIIPGSAADQDGRIQVNDQIIAVDGVNLQGFTNQEAVEVL 76
cpPDZ_EcRseP-like cd23081
circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and ...
 244-305 3.11e-03

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.


Pssm-ID: 467638 [Multi-domain]  Cd Length: 83  Bit Score: 37.17  E-value: 3.11e-03
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gi 1370465470 244 VIISRIVKGGAAEKSGLLhEGDEVLEINGIEIRgkDVNEVFDLLSDMHGT-LTFVLIPSQQIK 305
Cdd:cd23081     1 PVVGEVVANSPAAEAGLK-PGDRILKIDGQKVR--TWEDIVRIVRENPGKpLTLKIERDGKIL 60
PDZ3_DLG5-like cd06767
PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 217-276 3.90e-03

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467248 [Multi-domain]  Cd Length: 82  Bit Score: 36.54  E-value: 3.90e-03
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gi 1370465470 217 GETvKIVRIEKARDiPLGATVR-NEMDSVIISRIVKGGAAEKSGLLHeGDEVLEINGIEIR 276
Cdd:cd06767     1 EEP-RHVSIEKGSE-PLGISIVsGENGGIFVSSVTEGSLAHQAGLEY-GDQLLEVNGINLR 58
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
 316-375 4.18e-03

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 35.85  E-value: 4.18e-03
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gi 1370465470 316 VKAHFDYDPSD-DPyvpcrelgLSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVPG 375
Cdd:cd11827     2 CKALYAYDAQDtDE--------LSFNEGDIIEILKEDPSGWWTGRLRGKE------GLFPG 48
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
 337-374 4.30e-03

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 35.87  E-value: 4.30e-03
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gi 1370465470 337 LSFQKGDILHVISQE--DPNWWQAYREGDednqplAGLVP 374
Cdd:cd11866    16 LSFKRGDLIYIISKEydSFGWWVGELNGK------VGLVP 49
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
 337-362 4.55e-03

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 35.83  E-value: 4.55e-03
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gi 1370465470 337 LSFQKGDILHVISQEDPNWWQAYREG 362
Cdd:cd11806    16 LSFESGDKLLVLRKPSVDWWWAEHNG 41
RseP COG0750
Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, ...
 241-297 4.67e-03

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];


Pssm-ID: 440513 [Multi-domain]  Cd Length: 349  Bit Score: 39.68  E-value: 4.67e-03
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gi 1370465470 241 MDSVIISRIVKGGAAEKSGLLhEGDEVLEINGIEIrgKDVNEVFDLLSDMHG-TLTFV 297
Cdd:COG0750   127 LTPPVVGEVVPGSPAAKAGLQ-PGDRIVAINGQPV--TSWDDLVDIIRASPGkPLTLT 181
PDZ4_INAD-like cd23065
PDZ domain 4 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 ...
 225-287 4.73e-03

PDZ domain 4 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467278 [Multi-domain]  Cd Length: 82  Bit Score: 36.34  E-value: 4.73e-03
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gi 1370465470 225 IEKARD-IPLGATVRNEMDSV----IISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd23065     2 IELKTDkSPLGVSVVGGKNHVttgcIITHIYPNSIVAADKRLKVFDQILDINGTKVHVMTTLKVHQLF 69
PDZ2_GRIP1-2-like cd06681
PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 244-287 5.04e-03

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467169 [Multi-domain]  Cd Length: 89  Bit Score: 36.44  E-value: 5.04e-03
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gi 1370465470 244 VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLL 287
Cdd:cd06681    32 LTVTHVRPGGPADREGTIKPGDRLLSVDGISLHGATHAEAMSIL 75
PDZ_rhophilin-like cd06712
PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 221-291 5.06e-03

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467196 [Multi-domain]  Cd Length: 78  Bit Score: 36.41  E-value: 5.06e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370465470 221 KIVRIEKaRDIPLGATVRNemDS-VIISRIVKGGAAEKSGlLHEGDEVLEINGIEIRGKDVNEVFDLLSDMH 291
Cdd:cd06712     2 RTVHLTK-EEGGFGFTLRG--DSpVQVASVDPGSCAAEAG-LKEGDYIVSVGGVDCKWSKHSEVVKLLKSAG 69
PDZ_PDLIM-like cd06753
PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 244-298 5.38e-03

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 PDZ domains). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDLIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467235 [Multi-domain]  Cd Length: 79  Bit Score: 36.35  E-value: 5.38e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370465470 244 VIISRIVKGGAAEKSGLLhEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVL 298
Cdd:cd06753    24 LTISRVTPGGKAAQANLR-PGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTL 77
PDZ6_MUPP1-like cd06670
PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 220-277 6.06e-03

PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of multi-PDZ-domain protein 1 (MUPP1). MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ6 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467158 [Multi-domain]  Cd Length: 87  Bit Score: 36.46  E-value: 6.06e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370465470 220 VKIVRIEKARDiPLGATVRNEMDS--VIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRG 277
Cdd:cd06670     4 ERTITIVKGNS-SLGITVSADKDGngCIVKSIIHGGAVSRDGRISVGDFIVSINNESLRN 62
PDZ2_Dlg1-2-4-like cd06724
PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 243-273 6.51e-03

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467207 [Multi-domain]  Cd Length: 85  Bit Score: 36.09  E-value: 6.51e-03
                          10        20        30
                  ....*....|....*....|....*....|.
gi 1370465470 243 SVIISRIVKGGAAEKSGLLHEGDEVLEINGI 273
Cdd:cd06724    29 GIYVTKIIEGGAAQKDGRLQVGDKLLAVNDV 59
PDZ3_FL-whirlin-like cd06742
PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of ...
 234-283 6.87e-03

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467224 [Multi-domain]  Cd Length: 91  Bit Score: 36.18  E-value: 6.87e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370465470 234 GATVRNEMDSVIisRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEV 283
Cdd:cd06742    20 GANTKQPLPRVI--NIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREA 67
degP_htrA_DO TIGR02037
periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various ...
 244-276 7.60e-03

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 273938 [Multi-domain]  Cd Length: 428  Bit Score: 39.13  E-value: 7.60e-03
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1370465470 244 VIISRIVKGGAAEKSGlLHEGDEVLEINGIEIR 276
Cdd:TIGR02037 259 ALVAQVLPGSPAEKAG-LKAGDVITSVNGKPIS 290
PRK14981 PRK14981
RNA polymerase Rpb4 family protein;
560-592 8.40e-03

RNA polymerase Rpb4 family protein;


Pssm-ID: 184943  Cd Length: 112  Bit Score: 36.38  E-value: 8.40e-03
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1370465470 560 IIFIAPPSQERLRALLAKEGKNPKPEELREIIE 592
Cdd:PRK14981   73 IADILPETRDELRAIFAKERYTLSPEELDEILD 105
SH3_RUSC1 cd11958
Src homology 3 domain of RUN and SH3 domain-containing protein 1; RUSC1, also called NESCA ...
 334-374 8.52e-03

Src homology 3 domain of RUN and SH3 domain-containing protein 1; RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212891 [Multi-domain]  Cd Length: 51  Bit Score: 34.81  E-value: 8.52e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1370465470 334 ELGLSFQKGDILHVISQEDPNWWQAyREGDEDnqplaGLVP 374
Cdd:cd11958    12 ESQLSFRKGEELQVLGTVDEDWIRC-RRGDRE-----GLVP 46
PDZ_LIMK-like cd06754
PDZ domain of LIM Kinase (LIMK) family, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 261-294 8.55e-03

PDZ domain of LIM Kinase (LIMK) family, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the LIMK protein family, and related domains. The LIMK family is composed of LIMK1 and LIMK2, which are common downstream effectors of several signalization pathways and function as signaling nodes that control cytoskeleton dynamics through the phosphorylation of cofilin family proteins. They also control microtubule dynamics. The LIMK1 PDZ domain binds tubulin and nischarin. LIMK1 also binds a carboxy-terminal motif of membrane type 1-matrix metalloproteinase (MT1-MMP, also known as MMP14) having features of a PDZ domain-binding site; MT1-MMP is a major protease involved in dissemination of carcinoma cells during cancer progression. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LIMK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467236 [Multi-domain]  Cd Length: 92  Bit Score: 36.09  E-value: 8.55e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1370465470 261 LHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTL 294
Cdd:cd06754    51 LHVGDRILEVNGTPVRDLSLEEIDDLIQSTSKTL 84
PDZ_SYNPO2-like cd10820
PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related ...
 246-295 8.62e-03

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNPO2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467264 [Multi-domain]  Cd Length: 78  Bit Score: 35.75  E-value: 8.62e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370465470 246 ISRIVKGGAAEKSGLLhEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLT 295
Cdd:cd10820    26 VAKIRKKSKAALAGLC-EGDELLSINGKPCADLSHSEAMDLIDSSGDTLQ 74
SH3_RUSC1_like cd11810
Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that ...
 329-374 9.62e-03

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212744  Cd Length: 50  Bit Score: 34.73  E-value: 9.62e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1370465470 329 YVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEdnqplaGLVP 374
Cdd:cd11810     8 HVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTK------GLVP 47
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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